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PREGNANCY AND DRUG METABOLISM
380 ages of the offenders or to draw comparisons earlier with years, and there is no indication when treatment was made a condition of a probation order.. More information about the 398 hospital orders would also have been welcome. Society’s response to crime is to be found in the report of the Chief Inspector of Constabulary.2 Though more crimes were cleared up than ever before, the proportion solved fell slightly to 39-2%. There are more vacancies
analyse the
conclusions to be drawn. Furthermore, the urine pH of their subjects was apparently not regulated, although has been shown to be very important in studies of drug excretion, particularly of pethidine.14 15 The finding suggest that pregnancy and oral contraceptives reduce the ability to metabolise these drugs, but adequately controlled studies are needed to confirm this. A similarity between theeffects of pregnancy and oral contraceptives on metabolic processes has already been noted: both interfere with the transport of substances such as bromsulphthalein through the liver cell, 16 11 and both are associated witha rise in coagulation factors.18 It has, in fact, been sug. gested that oral contraceptives produce a state of pseudo. pregnancy."We do not know whether pregnant women and those taking oral contraceptives are particularly susceptible to pethidine and phenothiazines. Isolated cas’e-reports have described the collapse of obstetric patients after intravenous and intramuscular pethidine and .promazine,2o 22 but they give no real indication that this hazard is more- common in pregnancy.
this
-
for a
police
officers than
ever
before
(about 8000), despite
rising number -of officers in post. Only 1 in 70 of recruits,
had
two or more
passes in the G.c:E, at A level.
The cour-
age and integrity of the, police come.out of this report well;. and the awards for bravery make astonishing reading; but
it is evident that the Force is not attracting its fair share of brains. This is sad, for intelligence is crucial in the war against crime, as in any other war.
PREGNANCY AND DRUG METABOLISM
THE effects of drugs may differ at various stages of life, and this is often due to differences in metabolism. For example, in the premature and newborn infant chlor-
amphenicol may produce vomiting, cyanosis, hypothermia, and vascular collapse because of a deficiency or immaturity of the enzyme glucuronyl transferase, which is necessary for its conjugation with glucuronic acid.3 Immaturity of acetylation mechanisms may be responsible for the kernicterus which sometimes accompanies sulphonamide therapy in the newborn.4 Vitamin Ki5 and novobiocin 6 may also cause hyperbilirubinaemia and kernicterus in these -infants. Tetracyclines may produce abnormalities of bone structure and growth in the foetus and newborn,’7 as well as apparently permanent discoloration and even dysplasia of the deciduous teeth. 8 At the other end of life, elderly patients are more susceptible to digitalis
A SUCCESSFUL
.’
intoxication.9
Pregnancy also
appears to influence
drug metabolism.
found that serum-cholinesterase levels are relatively low at term, suggesting that susceptibility to the action of suxamethonium is increased at this time. Discussing the relation between fatty degeneration of the liver and tetracycline therapy in pregnancy, Kunelis et a1.l! suggested that the increased demand forprotein anabolism during pregnancy may make the liver more sensitive to drugs such as tetracycline, which depress this function. King- 12 found that pregnant rats have higher brain and blood levels of pentobarbitone than non-pregnant rats after a standard dose. Crawford and Rudofsky 13 studied the pattern of urinary excretion of metabolites of pethidine and promazine in normal subjects, pregnant and postmenopausal women, and women taking oral contracept,ives; but unfortunately their subjects were few, and the variability of excretion was too wide to allow any firm Shnider
2.
10
Report of Her Majesty’s Chief 1965. H.M.
Stationery Office.
Inspector
of
Constabulary
SINCE Wilson and Atkinson showed in 1945 23 that the staphylococci current in man could be classified by their reaction to a limited number of bacteriophages, the method has become one of the main tools of the hospital epidemiologist. Judged by the one or more phages which lyse the growing staphylococci, these may be assigned to one of three main groups, and, the pattern of lysis within each group allows a strain,to be identified with reasonable accuracy. Within the past twenty years staphylococci have had such attention as they never had before, and it may be a matter of remark that the number of new types identified by bacteriophage during this period has not increased by more than a few. It is true that most attention has been paid to the few phage-types which appear to spread most readily and which cause the more serious infections. Most of these are resistant to one or more of the commonly used antibiotics, and in any hospital the appearance of any of these is a danger signal. In 1960 workers in England, North America, and Australia noticed an increase in the number of apparently pathogenic strains which were not lysed by any available bacteriophage. Jevons and Parker 24 suggested that these untypable strains had arisen from the phage-type 83Aitself identified not long before-by lysogenisation witha phage which blocked lysis by phage 83A. Not long after this Willis and his colleagues 25 26 showed that these resistant strains had cultural characteristics which differ from those of the majority of staphylococci in circulation They form yellow colonies on glycerol-monoacetate agar-
they seldom hydrolyseTween 80 ’or produce staphylokinase, but most of them produce a &bgr;-lysin. To this M., London, D. R., Milne, M. D., Simenhoff, M. L. Br Pharmac. Chemother. 1963, 20, 285.
14. Asatoor, A.
for the Year
8s.
3. Br. med. J. 1961, ii, 947. 4. Odell, G. B. J. Pediat. 1959, 55, 268. 5. Cohlan, S. Q. N.Y. St. J. Med. 1964, 64, 493. 6. Sutherland, J. M., Keller, W. H. Am. J. Dis. Child. 1961, 101, 447. 7. Cohlan, S. Q., Bevelander, G., Tiamsic, T. ibid. 1963, 105, 453. 8. Lancet, 1965, ii, 71; ibid. 1966, i, 917. 9. Schott, A. Post-Grad. med. J. 1964, 40, 628. 10. Shnider, S. M. Anesthesiology, 1965, 26, 335. 11. Kunelis, C. T., Peters, J. L., Edmondson, H. A. Am. J. Med. 1965, 38, 359. 12. King, J. E. Am. J. Obstet. Gynec. 1964, 89, 1019. 13. Crawford, J. S., Rudofsky, S. Br. J. Anœsth. 1966, 38, 446.
PARASITE
15. 16. 17.
Lancet, 1966, i, 1256. Mueller, M. N., Kappas, A. J. clin. Invest. 1964, 43, 1905. Kleiner, G. J., Kresch, L., Arias, I. M. New Engl. J. Med. 1965, 273 420.
18. .19. 20. 21. 22. 23. 24. 25. 26.
Poller, L., Thomson, J. M. Br. med. J. 1966, ii, 23. Tyler, E. T. ibid. 1964, ii, 843. Amias, A. G., Fairbairn, D. ibid. 1963, ii, 432. O’Meara, D. J. P. ibid. p. 749. Donaldson, I. A. ibid. p. 1592. Wilson, G. S., Atkinson, J. D. Lancet, 1945, i, 647. Jevons, M. P., Parker, M. T. J. clin. Path. 1964, 17, 243. Willis, A. T., Jacobs, S. I., Goodburn, G. M. Lancet, 1963, ii, 67 Willis, A. T., Jacobs, S. I., Goodburn, G. M. J. Path. Bact. 1964, 87, 155
analyse the
conclusions to be drawn. Furthermore, the urine pH of their subjects was apparently not regulated, although has been shown to be very important in studies of drug excretion, particularly of pethidine.14 15 The finding suggest that pregnancy and oral contraceptives reduce the ability to metabolise these drugs, but adequately controlled studies are needed to confirm this. A similarity between theeffects of pregnancy and oral contraceptives on metabolic processes has already been noted: both interfere with the transport of substances such as bromsulphthalein through the liver cell, 16 11 and both are associated witha rise in coagulation factors.18 It has, in fact, been sug. gested that oral contraceptives produce a state of pseudo. pregnancy."We do not know whether pregnant women and those taking oral contraceptives are particularly susceptible to pethidine and phenothiazines. Isolated cas’e-reports have described the collapse of obstetric patients after intravenous and intramuscular pethidine and .promazine,2o 22 but they give no real indication that this hazard is more- common in pregnancy.
this
-
for a
police
officers than
ever
before
(about 8000), despite
rising number -of officers in post. Only 1 in 70 of recruits,
had
two or more
passes in the G.c:E, at A level.
The cour-
age and integrity of the, police come.out of this report well;. and the awards for bravery make astonishing reading; but
it is evident that the Force is not attracting its fair share of brains. This is sad, for intelligence is crucial in the war against crime, as in any other war.
PREGNANCY AND DRUG METABOLISM
THE effects of drugs may differ at various stages of life, and this is often due to differences in metabolism. For example, in the premature and newborn infant chlor-
amphenicol may produce vomiting, cyanosis, hypothermia, and vascular collapse because of a deficiency or immaturity of the enzyme glucuronyl transferase, which is necessary for its conjugation with glucuronic acid.3 Immaturity of acetylation mechanisms may be responsible for the kernicterus which sometimes accompanies sulphonamide therapy in the newborn.4 Vitamin Ki5 and novobiocin 6 may also cause hyperbilirubinaemia and kernicterus in these -infants. Tetracyclines may produce abnormalities of bone structure and growth in the foetus and newborn,’7 as well as apparently permanent discoloration and even dysplasia of the deciduous teeth. 8 At the other end of life, elderly patients are more susceptible to digitalis
A SUCCESSFUL
.’
intoxication.9
Pregnancy also
appears to influence
drug metabolism.
found that serum-cholinesterase levels are relatively low at term, suggesting that susceptibility to the action of suxamethonium is increased at this time. Discussing the relation between fatty degeneration of the liver and tetracycline therapy in pregnancy, Kunelis et a1.l! suggested that the increased demand forprotein anabolism during pregnancy may make the liver more sensitive to drugs such as tetracycline, which depress this function. King- 12 found that pregnant rats have higher brain and blood levels of pentobarbitone than non-pregnant rats after a standard dose. Crawford and Rudofsky 13 studied the pattern of urinary excretion of metabolites of pethidine and promazine in normal subjects, pregnant and postmenopausal women, and women taking oral contracept,ives; but unfortunately their subjects were few, and the variability of excretion was too wide to allow any firm Shnider
2.
10
Report of Her Majesty’s Chief 1965. H.M.
Stationery Office.
Inspector
of
Constabulary
SINCE Wilson and Atkinson showed in 1945 23 that the staphylococci current in man could be classified by their reaction to a limited number of bacteriophages, the method has become one of the main tools of the hospital epidemiologist. Judged by the one or more phages which lyse the growing staphylococci, these may be assigned to one of three main groups, and, the pattern of lysis within each group allows a strain,to be identified with reasonable accuracy. Within the past twenty years staphylococci have had such attention as they never had before, and it may be a matter of remark that the number of new types identified by bacteriophage during this period has not increased by more than a few. It is true that most attention has been paid to the few phage-types which appear to spread most readily and which cause the more serious infections. Most of these are resistant to one or more of the commonly used antibiotics, and in any hospital the appearance of any of these is a danger signal. In 1960 workers in England, North America, and Australia noticed an increase in the number of apparently pathogenic strains which were not lysed by any available bacteriophage. Jevons and Parker 24 suggested that these untypable strains had arisen from the phage-type 83Aitself identified not long before-by lysogenisation witha phage which blocked lysis by phage 83A. Not long after this Willis and his colleagues 25 26 showed that these resistant strains had cultural characteristics which differ from those of the majority of staphylococci in circulation They form yellow colonies on glycerol-monoacetate agar-
they seldom hydrolyseTween 80 ’or produce staphylokinase, but most of them produce a &bgr;-lysin. To this M., London, D. R., Milne, M. D., Simenhoff, M. L. Br Pharmac. Chemother. 1963, 20, 285.
14. Asatoor, A.
for the Year
8s.
3. Br. med. J. 1961, ii, 947. 4. Odell, G. B. J. Pediat. 1959, 55, 268. 5. Cohlan, S. Q. N.Y. St. J. Med. 1964, 64, 493. 6. Sutherland, J. M., Keller, W. H. Am. J. Dis. Child. 1961, 101, 447. 7. Cohlan, S. Q., Bevelander, G., Tiamsic, T. ibid. 1963, 105, 453. 8. Lancet, 1965, ii, 71; ibid. 1966, i, 917. 9. Schott, A. Post-Grad. med. J. 1964, 40, 628. 10. Shnider, S. M. Anesthesiology, 1965, 26, 335. 11. Kunelis, C. T., Peters, J. L., Edmondson, H. A. Am. J. Med. 1965, 38, 359. 12. King, J. E. Am. J. Obstet. Gynec. 1964, 89, 1019. 13. Crawford, J. S., Rudofsky, S. Br. J. Anœsth. 1966, 38, 446.
PARASITE
15. 16. 17.
Lancet, 1966, i, 1256. Mueller, M. N., Kappas, A. J. clin. Invest. 1964, 43, 1905. Kleiner, G. J., Kresch, L., Arias, I. M. New Engl. J. Med. 1965, 273 420.
18. .19. 20. 21. 22. 23. 24. 25. 26.
Poller, L., Thomson, J. M. Br. med. J. 1966, ii, 23. Tyler, E. T. ibid. 1964, ii, 843. Amias, A. G., Fairbairn, D. ibid. 1963, ii, 432. O’Meara, D. J. P. ibid. p. 749. Donaldson, I. A. ibid. p. 1592. Wilson, G. S., Atkinson, J. D. Lancet, 1945, i, 647. Jevons, M. P., Parker, M. T. J. clin. Path. 1964, 17, 243. Willis, A. T., Jacobs, S. I., Goodburn, G. M. Lancet, 1963, ii, 67 Willis, A. T., Jacobs, S. I., Goodburn, G. M. J. Path. Bact. 1964, 87, 155